Preparation of 9(11)-dehydro-12-desoxy sapogenins



United States Patent 3,170,921 PREPARATION ()F 9(11)-DEHYDRO-12-DESOXYSAPOGENINS Joseph Elks, London, Gordon Hanley Phillipps, Greenford,Dennis Edward Clark, Worthing, David Arthur Thomas, Pinner, and LeslieStephenson, Hanwell, Lon don, England, assignors to Glaxo LaboratoriesLimited, Greenford, England, a British company No Drawing. Filed July 5,1963, Ser. No. 293,172 Claims priority, application Great Britain, Aug.17, 1962, 31,720/ 62 19 Claims. (Cl. 260-23955) This invention isconcerned with improvements in or relating to steroids and is inparticular concerned with the preparation of 9(11)-dehydro-steroids and3-esters thereof.

Sapogenins represent an important group of starting materials for theproduction of anti-inflammatory and other pharmacologically activesteroids due to their occulrence an plants as their glycosides(sapogenins), However in order to utilise the sapogenins for thispurpose it is necesary to subject them to various transformation stepsin order to obtain intermediates having functional groups correspondingto the desired end products. The present invention is thus concernedwith a sequence of steps involving the conversion of a9(11)-dehydrothereof, to the corresponding 9-(11)- lehydro-l2-desoxy12-keto steroid, particularly a sapogenin or a 3-ester compound, thelatter being an important intermediate in the preparation of activesteroids having C-n'ng substituents e.g. 9a-fluoro and 'llfi-hydroxy.

"ice

' ticularly a sapogenin or a 3-ester thereof, to form a 9(11)-dehydro-l2(0: or ;8)-hydroxy-steroid or a mixture of the l2-hydroxy epimers (thereduction preferably being effected with a borohydride or aluminumhydride of an alkali metal or an alkaline earth metal) and thereafter,if desired, converting the 12-hydroxy product to a 12-acylate e.g.12-acetate.

(B) converting the product'of A to the 12-halogeno (i.e. chloro orbromo) compound either as an individual epimer or a mixture of epimers,preferably by reaction with the appropriate hydrogen halide,

(C) reducing the product of B to form a 9(11)-dehydro-12-desoxy steroid.I

We have found that the aforesaid sequence can be efiected in goodoverall yield.

It should be noted that the stage C of the above sequence is per senovel and useful and is included Within the scope of the invention as 'aseparate embodiment.

Since hecogenin is a most important 12-keto steroid the invention willnow be particularly described with reference to 9(11)-dehydro-hecogeninbut it should be understood that the invention is not limited to the useof hecogenin derived starting materials the invention being, forexample, also applicable to the transformation of other 9(11)-dehydrosteroids e.g. 9(11)-dehydro botogenin.

Schematically, in the case of 9(11)-dehydro-hecogenin, the invention maythus be represented as follows:

Wit

wherein R is a hydrogen atom or an acyl group and X is a-chlorine orbromine atom.

Stage A.Reduction of 9(11)-dehydr0hecogenin (I). to the epimeric9(11)-dehydra-12-hydroxy compounds (II) and (III) As stated above, thisreaction is preferably effected with a borohydride-or an aluminiumhydride of an alkali metal or an alkaline earth metal of which group ofcompounds we find it convenient to use sodium borohydride. The startingsteroid may be the 3-hydroxy or a 3-acyloxy compound and if the latteris used then, depending onthe reaction conditions, the 3-acyloxy groupmay or may not be hydrolysed. From the point of view of overallefiiciency of the process, it would seem to make little differencewhether one starts with a 3-.acyloxy compound and Whether or not this ishydrolysed in situ.

Reduction with borohydrides other than lithium borohydride is preferablyeffected in a lower alkanol or a technical grade thereof such asindustrial methylated spirit, the alkanol being, if desired, admixedwith water. In order to improve the solubility of the steroid in thesolvent this may contain a proportion of a cyclic ether e.g. dioxan ortetrahydrofuran. The borohydride will in general be used in excess ofthat theoretically required to effect the reduction and the reductionmay conveniently be effected at a temperature ranging from ambienttemperature to the reflux temperature of the solvent. The 3-acyloxygroup, if present, may be hydrolysed during the reaction.

Lithium borohydride should be used in a non-hydroxylic solvent of whichthe cyclic ethers such as dioxan and tetrahydrofuran are preferred,otherwise reaction'conditions will be as for other borohydrides.

The aluminium hydrides, particularly lithium aluminium hydride, reactmore vigorously than the borohydrides and the reduction should beeffected in a non-hydroxylic solvent e.g. a cyclic ether such as dioxanor tetrahydrofuran otherwise the reaction conditions are similar tothose used for the borohydrides.

The reduction product may then be acylated to provide the correspondingIZ-acylates but on reaction in Stage B these will lead to a 123-halogeno steroid as stated below.

The product of reduction of A will generally be a mixture of epimerswhich behave similarly in subsequent reactions and there is no advantageto be gained in separating them. Consequently one will in general usethe epimeric mixture as the starting product for Stage B.

Stage B.-Conversin of epimeric 9(I1)-dehydro-12-hydroxy compounds (II)and (III) into the 12a-lzalogen0 epimer (IV) and the IZB-halbgeno-epimer(V) This reaction is conveniently effected by reaction with theappropriate hydrogen halide, for example by adding a solution of thehydrogen halide in an inert organic solvent to a solution of the productof Stage A in an inert organic solvent. Whether one starts With the 126-01 (II) or the IZu-Ol (III) or a mixture thereof, the first product ofreaction with the hydrogen halide is the 12ot-halogeno compound (IV).However in the presence of hydrogen halide it tends to epimerize to themore stable 12,8-epirner (V) though the rate depends markedly on thesolvent. Epimerization appears to be encouraged in polar solvents, e.g.lower alkanols, and in the presence of such solvents it may be difficultto stop the reaction at the l2a-halogeno stage. Epimerization is veryrapid and substantially complete with methanol but not quite so completewith ethanol although the rate of reaction is reasonably fast, IflZa-epimers are desired the reaction should preferably be effected in anon-polar organic solvent e.g. benzene or carbon tetrachloride. 7

One may thus, if desired, produce either the l2ocor 12,6-halogenocompounds either of which, or a mixture thereof, may be used in the nextstage.

The reaction can be effected at a temperature in the range of 050 C. butis conveniently effected at ambient temperature. Normally one will use alarge excess of hydrogen halide.

Where the 12 (a or /3)-hydroxy product of Stage A is converted to a 12(as or [3)-acylate it should be noted that the reaction product of StageB will be a 12,8-halogeno steroid.

The reaction may be effected in the presence or absence of a 3-acyloxygroup but if this is present it may be hydrolysed during the reaction.The free hydroxy compounds (IV) and (V) can be acylated prior to Stage Chut apart from permitting this to be effected at a rather higherconcentration in certain solvents it is not particularly advantageous.

Stage C.-Reducti0n of epimeric 9(11)-dehydr0-12-halogeno compounds (IV)and (V) 10 9(1] )dehydr0tig0- genin (VI) Either of the l2-halogenoepimers as 35-01 or 3-acylate can then be reduced to9(l1)-dehydrotigogenin or a 318- acylate. The reduction is preferablyeffected in solution or suspension in an inert organic solventcontaining a base e.g. a tri- (lower alkyl) amine or an alkali metalsalt,

of a lower alkanoic acid, e.g. sodium acetate, by catalytichydrogenolysis, for example using a palladium hydrogenation catalyst orRaney nickel. Suitable solvents include ethyl acetate, tetrahydrofuran,enzene and dimethylformamide.

' In place of catalytic hydrogenolysis one may effect reduction by meansof an alkali metal or alkaline earth metal in liquid ammonia, a primaryamine containing 1-5 carbon atoms or a polymethylene diamine.

By operating according to the preferred aspects of the process accordingto the invention we have been able to obtain very high overall yields of9(11)-dehydrotigogenin by avoiding purification of the intermediates.The resulting material appears to be of good quality and in particulardoes not appear to be contaminated by ll-dehydrotigogenin.

The invention also includes within its .scope compounds of the generalformula wherein X is a chlorine or bromine atom and R is a hydrogen atomor an acyl group e.g. a lower alkanoyl oup. In order that the inventionmay be well understood the following examples are given by way ofillustrationonly. In the examples optical rotations were determined asea. 1% solutions in chloroform.

EXAMPLE l-STAGE A Reductiton of 9(-1J )-dehydrohecogenin acetate (I)With sodium borohydride in refluxing aqueousethanl.9(ll)-dehydrohecogenin acetate (40 g.) suspended in ethanol (500ml.) was warmed to ca. 40 and treated with a solution of sodiumborohydride (10 g.) in water (50 ml.). The mixture was boiled underreflux for 4 hr. Water (200 ml.) was then added and the solution wasconcentrated under reduced pressure to ca. 400 ml. More water (1 litre)was added and the mixture was allowed to stand at for 2 hr. The productwas filtered ofi, dried in vacuo at 60 overnight to yield a mixture of 9l l )-dehydrorockogenin and 9 1 l )-dehydro-epirockogenin (36.3 g.,99%), M.P. 204-208, [0:] 68.3.

The crude diol (6 g.) was chromatographed on magnesium trisilicate (240g.) made up in benzene. Elution with 5% ethyl acetate in benzene andsubsequent crystallization from acetone gave 9(1l)-dehydrorockogenin(3.9 g.), M.P. 208-2l2, [M 75. (An analytical sample had C, 75.6; H,9.7. Calc. for C H C C, 75.3; H, 9.8%.)

Elution with ethyl acetate and subsequent crystallization from methanolgave 9(ll)-dehydro-epirockogenin (0.35 g.), M.P. 216-218. (An analyticalsample had C, 75.1; H, 9.65. Calc. for C H O C, 75.3; H, 9.8%).

Acetylation of 9(11)-dehydrorockogenin (36 g.) with acetic anhydride andpyridine at 100 for 1% hr. and subsequent crystallization from ether/hexane gave 9(1 1)- dehydrorockogenin diacetate (30.5 g.), M.P. 183-185,[ab 108.9. (Found: C, 72.1; H, 9.0. Calc. for C H O C, 72.3; H, 9.0%.)

Acetylation of 9(ll)-dehydro-epirockogenin under the same conditions andsubsequent crystallization from methanol gave the correspondingdiacetate, M.P. 169- l70, [a1 +67. (Found: C, 72.5; H, 9.1. C H Orequires C, 72.3; H, 9.0%.)

(II) With sodium borohydride in methanol-tetrahya'rofuran at roomtemperature-9Ul)-dehydrohecogenin acetate (0.5 g.) and sodiumborohydride (0.1 g.) in a mixture of tetrahydrofuran (3 ml.) and drymethanol (3 ml.) were left at room temperature for 1% The reactionproduct was poured into water, the solid collected and dried to give amixture of the 3-acetates of 9(ll)- dehydrorockogenin and 9 l1)-dehydro-epirockogenin (0.49 g.), M.P. 206-2l2, [a] 67.

A similar mixture (5.88 g.) was chromatographed on magnesium trisilicate(240 g.) made up in benzene. Elution with 2-5% ethyl acetate in benzeneand subsequent crystallization from methanol gave9(ll)-dehydrorockogenin 3-mono-acetate (3.65 g.), M.P. 242-245 [04] 71.(Found: C, 73.9; H, 9.4. C H O requires C, 73.7; H, 9.4%.)

Elution with 50% ethyl acetate in benzene and subsequent crystallizationfrom methanol gave 9(1l)-dehydroepirockogenin 3-mono-acetate (0.19 g.),M.P. 223228, [0:1 20-. (Found: C, 73.5; H, 9.1. C H O requires C, 73.7;H, 9.4%.)

(III) With lithium borohydride in tetrahydrofuran.- A solution of9(l1)-dehydrohecogenin acetate (0.5 g.) and lithium borohydride (0.25g.) in tetrahydrofuran (10 ml.) was boiled under reflux for 1 hr. Thereaction mixture was cooled and poured into water. The solid wascollected and dried to give a mixture of 9(11)-dchydrorockogenin and its12a-epimer (0.43 g.), [ab -62".

6 EXAMPLE 2-STAGE B Preparation of 12aand 12 8-chloro-5ot,25D-spirost-9(11)-en-3fl-0l and their acetates (I) A solution of9(1l)-dehydrorockogenin (5.2 g.) in'chloroform ml.) was saturated at,l0with dry hydrogen chloride gas and allowed to stand at room temperaturefor 30 min. Evaporation in vacuo and trituration of the residue withether gave l2oc-ChlOl05a,25D- spirost-9(1l)-en-3fi-ol (5.7 g.), M.P.133-134", [u] +202". (Found, on an analytical sample: C, 72.6; H, 9.3;Cl, 7.8. C2'1H41C103 requires C, 72.2; H, 9.2; Cl, 7.9%.)

Acetylation overnight at room temperature with pyridine and aceticanhydride and subsequent crystallisation from acetone gave thecorresponding 3-acetate, M.P. 202-205", [uJ 54-53". (Found: C, 71.1; H,8.7; Cl, 7.2. C H ClO requires C, 70.9; H, 8.8; Cl, 7.2%.)

(H) A 9.8 N solution of hydrogen chloride in dry methanol (53 ml.) wasadded slowly with stirring to a cooled suspension of9(l1)-dehydrorockogenin (5 g.) in dry methanol (48 ml.). After ca. 17hr. at room temperature the suspension was added to Water and the solidwas collected and dried, giving 1Zfl-chloro-5a,25D-spirost-9(ll)-en-3fl-ol 5.12 g., 98.5%), M.P. 206-208 [0.1 -93. (Found: on ananalytical sample: C, 71.8; H, 9.2; Cl, 8.1 C H ClO 'requires C, 72.2;H, 9.2; CI, 7.9%.)

Acetylation overnight at room temperature with pyridine and aceticanhydride and subsequent crystallisation from acetone gave thecorresponding 3-acetate, M.P. 174- 176, [ab 83. (Found: C, 71.15; H,9.0; Cl, 6.9. C H ClO requires C, 70.9; H, 8.8; Cl, 7.2%.)

(111) An 11 N solution of hydrogen chloride in dry methanol ml.) wasadded over 5 min. with stirring to a cooled suspension of a mixture of9(l1)-dehydrorockogenin and 9(ll)-dchydro-epirockogenin (18 g.) in drymethanol ml.). After 18 hr. at room tempera ture the suspension wasadded to Water (4 litres) and the solid was collected and dried.crystallisation from acetone gave 12,6 chloro 5 a25D-spirost-9(1l)-en-3fl-ol (11.6 g.), M.P. 204-207", decompi, [a] 95".

(IV) 9(11)-dehydrorockogenin 3-mono-acetate (1 g.) in dry, alcohol-freechloroform (20 ml.) was cooled and saturated with dry hydrogen chloride.After being left at room temperature for 1% hr., the reaction mixturewas evaporated in vacuo and the residue was crystallised from ether togive 3B-acetoxy-l2a-chloro-5a,25D-spirost- 9(l1)-en; M.P. 182-185, [ab!+45.5.

(V) An 11.4 N solution of hydrogen chloride in dry methanol (4.5 ml.)was added to'a cooled suspension of 9(1l)-dehydrorockogenin3-mono-acetate (0.5 g.) in dry methanol (5.5 ml.). The reaction mixturewas allowed to stand at room temperature overnight and, then it waspoured into water and the solid collected. Subsequent crystallisationfrom acetone' gave l2}8-chloro-5u,25D- spirost-9(ll)-en-3B-ol (0.35 g.),M.P. 201-204", [a1 96.

(VI) 9(ll)-dehydrorockogenin (1.3 g.) was dissolved in a saturatedsolution of hydrogen chloride in dry carbon tetrachloride and allowed tostand at room temperature for 1 hr. The reaction mixture was thenevaporated to dryness in vacuo giving 12a-chloro-5a,2SD-spirost-9(11)-en-3fi-ol (1.56 g.), [0:] ,+36.0.

(VII) An 11.7 N solution of hydrogen chloride in dry methanol (4.3 ml.)was added with stirring to a suspension of 9(ll)-dehydro-epirockogenin(0.5 g.) in dry methanol (5.7 ml.). After ca. 17 hr. at room temperaturethe suspension was poured into aqueous sodium hydrogen carbonate and thesolid was collected and dried to give12fi-chloro-5ot,25D-spirost-9(1l)-en-3,B-ol (0.51 g.), [e1 -91.5f.

(V111) A saturated solution of hydrogen chloride gas in dry ethanol (28ml.) Was added to a solution of 9(ll)- dehydro-epirockogenin (0.5 g.) indry ethanol (22 ml.)

a and the mixture was stirred at room temperature for 4 min. Thereaction mixture was then poured into aqueous sodium hydrogen carbonatesolution and the solid collected and dried to give12ot-chloro-5a,25Dspirost-9(11)-en- 35-01 (0.43 g.), [0119 t-l-27.

(IX) An 8.4 N solution of hydrogen chloride in dry methanol (6 ml.) wasadded with stirring to a suspension of 9(ll)-dehydrorockogenin diacetate(0.5 g.) in dry methanol (4 ml.). After 17 hr. at room temperature thesuspension was poured into water and the solid'collected and dried togive 12,3-ch1oro-5,25D-spirost-9(11)- en-3p-ol (0.415 g.), M.P. 206-208,[a] 90.3.

(X) 9(11)-dehydro-epirockogenin diacetate (0.5 g.) was treated as inExample 2 (IX) to give l2fi-chloroa,25D-spirost-9(l1)-en-3B-ol (0.42g.), M.P. 207- 209, [M -970.

EXAMPLE 3STAGE B J-br0m0-5a,25D-spirosI-9 (1 I -en-3,8-0l

EXAMPLE 4STAGE C Delzalogenation 0 120a and 1ZB-chlor05a,25D-spirost-9(11)-en-3/3-0l and their acetates (I) A mixture of 123-chloro-5u,25D-spirost-9(11)-en- 318-01 (10 g.), 5% palladium on carbon(1.0 g.), triethylamine (4.8 ml.) and tetrahydrofuran (110 ml.) washydrogenated at room' temperature and atmospheric pressure. Thehydrogenation was complete after 1 hr. The reaction mixture was thenfiltered and the filtrate was evaporated in vacuo to small bulk. Waterwas added and the sloid was collected to give crude9(l1)-dehydrotigogenin (9.27 g., 100%), M.P. l77l84, [ab --59.2.crystallisation of 9.0 g ofthis material from methanol gave9(11)-dehydrotigogenin (7.93 g., 88.3%), M.P. l87-'l90, [ab 59.'5. Asecond crop (D.357 g.) had M.P. 180-195, [a1 59.5. Total yield 92%.

(II) 12 8-chloro-5a,25D-spirost-9(ll)-en-3fi-ol (1 g.) was treated as inExample 4 (I) but with benzene (40 ml.) as solvent to give, aftercrystallisation from methanol, 9(1l)-dehydrotigogenin (81%), M.P.185-188", [a] 59.5. A second crop had M.P. 181-184 Total yield 88%.

(III) 12/3-chloro-5a,25D-spirost-9(ll-en-3/3-ol (4.6 g.) was treated asin Example 4 (I), but with ethyl acetate (690 ml.) as solvent, to give,after crystallisation from methanol, 9(l1)-dehydrotigogenin (87.5%),M.P. 188- 190, [11],; -59". A second crop had M.P. 179-182, [a] 58.5.Total yield 94.5%.

(IV) lZfl-chloro-5a,25D-spirost-9(11)-en-3,B-ol (l g.) was treated as inExample 4 (I), but with dimethylformamide ml.) as solvent to give, aftercrystallisation from methanol, 9(ll)-dehydrotigogenin (87% M.P. 187-189", [0:] 59". A second crop had M.P. 180484. Total yield 94%.

(V) 12/8-chloro-5a,25D-spirost-9(1l)-en-3;3-ol (0.5 g.) was treated asin Example 4 (I), but with ethanol (150 ml.) as solvent to give, aftercrystallisation from acetone, 9(l1)-dehydrotigogenin (70%), M.P.184-185, [uJ 57.5.

(VI) 1218 -chloro-5a,25D-spirost-9(ll)-en-3;3-ol (0.5 g.) was treated asinExample 4 (V), but with Raney nickel (ca. 2 g.) as catalyst to give,after crystallisation from methanol, 9(1l)-'dehydrotigogenin (57%), M.P.177-178, [a] 5'8.0.

(VII) A mixture of lZB-chloro-Sa,25D-spirost-9(ll)- en-3B-ol (0.5 g.),5% palladium on carbon (0.05 g.), fused sodium acetate (0.125 g.) andglacial acetic acid (40 ml.) was hydrogenated at room temperature andatmospheric pressure. The reaction mixture was filtered and the filtrateevaporated to low bulk. Water was added and the solid collected anddried to give 9(ll)-dehydrotigogenin (0.465 g.), [al 5 9.5.

(VIII) A mixture of 12a-chloro-5ot,25D-spirost-9(ll)- en-3fl-0l (5.65g.), 5% palladium on carbon (0.52 g.), triethylamine (1.66 ml.), andtetrahydrofuran (108 ml.) was hydrogenated at room temperature andatmospheric pressure. The reaction mixture was filtered and the filtratewas evaporated in vacuo to small bulk; water was added, and the solidwas collected and dried to give crude 9(l1)-dehydrotigogeni.n (4.85 g.,93%), M.P. 152l55, [M 45.7. Crystallisation from aqueous methanol gave9(11)-dehy-drotigogenin (3.34 g., 72%), M.P. 176- 178, [01],; 59.9.

(IX) A mixture of 3,8-acetoxy-12,B-chloro-5 x,25D- spirost-9(1l)-en (0.5g.), 5% palladium on carbon (0.05 g.), triethylamine (0.24 ml.), andethyl acetate (25 ml.) was hydrogenated at room temperature andatmospheric pressure. The hydrogenation was complete in 1 hr. Thereaction mixture was then filtered and the filtrate washed with water,dried and evaporated in vacuo. The residue (0.462 g.) was crystallisedfrom ethyl acetate to give 9(ll)-dehydrotigogenin acetate (0.409 g.,88%), M.P. 201-204", [ab -59".

(X) A mixture of 3B-acetoxy-l2a-chloro-5a,25D-spirost-9(l1)-en (0.5 g.),5% palladium on carbon (0.05 g.), triethylamine (0.24 ml.), and ethylacetate (75 ml.) was hydrogenated at room temperature and atmosphericpressure. The hydrogenation was complete in 3 hr. Isolation in the usualway and crystallisation from ethyl acetate gave 9(1l)-dehydrotigogeninacetate (0.389 g., 84%), M.P. 200203, [oc] -6l.

(XI) To a solution of sodium (0.56 g.) in liquid ammonia ml.) was addedover 5 min. a solution of chloro-5a,25D-spirost-9(11)-en3fi-ol (0.9 g.)in dry ether (50 ml.). After 30 min. stirring the excess sodium wasdestroyed wtih ammonium chloride and the ammonia was evaporated. Theresidue, after the addition of water, was extracted with chloroform. Theextract was washed with water, driedand evaporated in vacuo to givecrude 9(ll)-dehydrotigogenin (0.76 g.), M.P. 168-170". Acetylation ofthis product with acetic anhydride and toluene at 100 for 30 min. andsubsequent crystallisation from ethyl acetate gave9(l1)-dehydrotigogenin acetate (0.54 g., 59%), M.P.197-200", [0:1 61.5.

(XII) 1ZB-chloro-5a,25D-spirost-9(11)-en-3;8 01 (3.0 g.) was treated asin'Example 4(XI) to give crude 9(11)- dehydrotigogenin (2.865 g.), M.P.163-167". Acetylation and crystallisation from ethyl acetate gave 9(11)-hehydrotigogenin acetate (2.204 g., 72.0%), M.P. 193- 200.

EXAMPLE 5-STAGE C Dehalogenation of 1ZB-bromo-SaJSD-spirost- 9 (11en-SB-ol A mixture of 1Zfi-bromo-Sa,25D-spirost-9(l1)-en-3flol (1 g.),5% palladium on carbon (0.1 g.), triethylamine (0.32 ml.) and ethylacetate (100 ml.) was hydrogenated at room temperature and atmosphericpressure. The hydrogenation was complete in 1 hr. Isolation in the usualway and crystallisation from methanol gave 9(11) dehydrotigogenin (77%),M.P. '178-179, [a] 58.2.

We claim:

1. A process which comprises the steps of reducing a 9(11)-dehydro-12keto sapogenin to form a 9(ll)-dehydro-lZ-hydroxy sapogenin, convertingthe 12 hydroxy group to a 12-ha1ogeno group selected from the groupconsisting of IZ-chloro and 12-bromo groups and reducing the 12-halogenogroup to form a 9(ll)-dehydro- 12-desoxy sapogenin.

reaction with a hydrogen halide selected from the group consisting ofhydrogen chloride and hydrogen bromide.

5. A process as claimed in claim 4 wherein the reaction is etlected in alower alkanol.

6. A process as defined in claim 4 wherein the reaction is elfected at atemperature in the range of -50 C.

7. A process which comprises reducing a 9(1l)-dehydro- 12-halogenosapogenin, wherein the halogeno group is slected from the groupconsisting of chlorine and bromine atoms, to form a9(11)-dehydro-12-desoxy sapogenin.

8. A process as defined in claim 7 wherein the reduction of the9(11)-dehydro-12-halogeno sapogenin is effected by catalytichydrogenolysisgusing a catalyst selected from the group consisting ofpalladium and Raney nickel.

9. A process as claimed in claim 8 wherein the reaction is effected atleast partly in solution in an inertorganic] solvent containing a base.

10. A process as claimed in claim 7 wherein the reduction of the9(11)-dehydro-l2-halogeno sapogenin is effected by means of metalselected from the group consisting of alkali metals and alkaline earthmetals in a medium selected from the group consisting of liquid ammonia,primary amines containing 1-5 carbon atoms and polymethylene diamines. 7l1. Ina process for the production of a 9(11)-dehydro 12-desoxysapogenin from a 9(1l)-dehydro-12-keto sapogenin, the step whichcomprises reacting a 9(11)-dehydro- 12 hydroxy sapogenin with a hydrogenhalide selected from the group'consisting of hydrogen chloride andhydrogen bromide toform a 9(11)dehydro-12-halogeno sapogemn.

12. In a process for the production of a 9(11)-dehydrol2-desoxysapogenin from a 9(11)-dehydro-l2-keto-sapogenin, the step whichcomprises reducing a 9(11)-dehydro- 12-halogeno sapogenin, wherein thehalogeno group is selected from the group consisting. of chlorine andbromine atoms, by catalytic hydrogenolysis using a catalyst selectedfrom the group consisting of palladium and Raney nickel, to form a9(11)-dehydro-12-desoxy sapogenin.

13. A process which comprises the step-s of reducing a 9(11)-dehydrohecogenin 3-lower alkanoate with a reducing agent selected from thegroup consisting of alkali metal borohydrides, alkaline earth metalborohydrides, alkali metal hydrides and alkaline earth metal aluminiumhydrides to form a IZ-hydroxy compound selected from the groupconsisting of 9( ll)-dehydrorockogenin and 9(11)- dehydro epirockogenin,reacting said 12 hydroxy compound with a hydrogen halide selected iromthe group consisting of hydrogen chloride and hydrogen bromide to formthe corresponding IZ-halogeno compound and reducing said 12-halogenocompound by catalytic hydrogenolysis using a catalyst selected from thegroup consisting of palladium and Raney nickel, to form9(1l)-dehydrotigogenm.

14. A compound of the formula where X is selected from the groupconsisting of chlorine and bromine atoms'and R is selected from thegroup consisting of hydrogen and lower alkanoyl groups.

15. 1Zea-chloro-Su,25D-spirost-9 l 1 -en-3f3-ol.

17. l2 8-chloro-5o;,25D-spirost-9(11)-en-3,8-ol. 18.3,8-acetoxy-12B-chloro-5a,D-spirost-9(11)-en.

I 19. 12,8-bromo-5a,25D-spirost-9(11)-en-3fl-oll References Cited by theExaminer FOREIGN PATENTS 211,7ss 12/57 Australia.

1 LEVV'IS GOTTS, Primary Examiner.

1. A PROCESS WHICH COMPRISES THE STEPS OF REDUCING A 9(11)-DEHYDRO-12KETO SAPOGENIN TO FORM A 9(11)-DEHYDRO-12-HYDROXY SAPOGENIN, CONVERTINGTHE 12-HYDROXY GROUP TO A 12-HALOGENO GROUP SELECTED FROM THE GROUPCONSISTING OF 12-CHLORO AND 12-BROMO GROUPS AND REDUCING THE 12-HALOGENOGROUP TO FORM A 9(11)-DEHYDRO12-DESOXY SAPOGENIN.
 14. A COMPOUND OF THEFORMULA